Estimating thermohaline structures in the tropical Indian Ocean from surface parameters using an improved CNN model

Accurately estimating the ocean’s subsurface thermohaline structure is essential for advancing our understanding of regional and global ocean dynamics. In this study, we propose a novel neural network model based on Convolutional Block Attention Module-Convolutional Neural Network (CBAM-CNN) to simultaneously estimate the ocean subsurface thermal structure (OSTS) and ocean subsurface salinity structure (OSSS) in the tropical Indian Ocean using satellite observations. The input variables include sea surface temperature (SST), sea surface salinity (SSS), sea surface height anomaly (SSHA), eastward component of sea surface wind (ESSW), northward component of sea surface wind (NSSW), longitude (LON), and latitude (LAT). We train and validate the model using Argo data, and compare its accuracy with that of the original Convolutional Neural Network (CNN) model using root mean square error (RMSE), normalized root mean square error (NRMSE), and determination coefficient (R²). Our results show that the CBAM-CNN model outperforms the CNN model, exhibiting superior performance in estimating thermohaline structures in the tropical Indian Ocean. Furthermore, we evaluate the model’s accuracy by comparing its estimated OSTS and OSSS at different depths with Argo-derived data, demonstrating that the model effectively captures most observed features using sea surface data. Additionally, the CBAM-CNN model demonstrates good seasonal applicability for OSTS and OSSS estimation. Our study highlights the benefits of using CBAM-CNN for estimating thermohaline structure and offers an efficient and effective method for estimating thermohaline structure in the tropical Indian Ocean

Understanding the compound marine heatwave and low-chlorophyll extremes in the western Pacific Ocean

The western Pacific Ocean is the global center for marine biodiversity, with high vulnerability to climate change. A better understanding of the spatiotemporal characteristics and potential drivers of compound marine heatwaves (MHWs) and low-chlorophyll (LChl) extreme events is essential for the conservation and management of local marine organisms and ecosystems. Here, using daily satellite sea surface temperature and model-based chlorophyll concentration, we find that the climatological spatial distribution of MHW-LChl events in total days, duration, and intensity exhibits heterogeneous distributions. The southwest sections of the South China Sea (WSCS) and Indonesian Seas are the hotspots for compound events, with total MHW-LChl days that are more than 2.5 times higher than in the other sub-regions. Notably, there is a trend toward more frequent (> 4.2 d/decade), stronger (> 0.5), and longer-lasting (> 1.4 d/decade) MHW-LChl occurrences in the WSCS. The occurrence of compound MHW-LChl extremes exhibits remarkable seasonal differences, with the majority of these events transpiring during winter. Moreover, there are generally statistically significant increasing trends in MHW-LChl events for all properties on both seasonal and inter-annual timescales. Furthermore, we reveal that the total days of compound MHW-LChl extremes are strongly modulated by large-scale climate modes such as the El Niño-Southern Oscillation and Dipole Mode Index. Overall, pinpointing MHW-LChl hotspots and understanding their changes and drivers help vulnerable communities in better preparing for heightened and compounded risks to marine organism and ecosystems under climate change

A dead reckoning localization method for in-pipe detector of water supply pipeline: an application to leak localization

Urban water supply pipeline system integrity is important for the urban life. The aim of the study reported in this paper is to locate the water pipeline leaks by using an in-pipe detector. In this study, a mathematical model is extracted from an actual inspection system. By using the homogeneous transformation theory, transformation matrix which is from carrier to a reference coordinate system is deduced, and then the global transformation matrix is obtained to describe the detector’s posture. Through measuring the distance increment of each sample time step in carrier coordinate system, the cumulative distance result is calculated. After combining the data of the inertial measurement unit (IMU) and odometer, the leak can be located. To improve the accuracy of leak localization, the magnetic markers are implemented about one in each 1 km distance, which provide reference points to be used to compensate accumulative error during the localization process. Furthermore, a dead reckoning localization method combining data of a micro electro-mechanical IMU, three odometers, and magnetic markers is proposed. To verify above localization algorithm, a simulation case study is conducted with the artificial error generated by the white noise. The simulation results show that the dead reckoning algorithm can effectively provide leak locations with a reasonable uncertainty. Based on this, an experimental platform was built in this study. The experimental results show that the relative error of leak locating achieves a reasonably good performanc

Endothelium- targeted overexpression of Krüppel- like factor 11 protects the blood- brain barrier function after ischemic brain injury

Microvascular endothelial cell (EC) injury and the subsequent blood- brain barrier (BBB) breakdown are frequently seen in many neurological disorders, including stroke. We have previously documented that peroxisome proliferator- activated receptor gamma (PPARγ)- mediated cerebral protection during ischemic insults needs Krüppel- like factor 11 (KLF11) as a critical coactivator. However, the role of endothelial KLF11 in cerebrovascular function and stroke outcome is unclear. This study is aimed at investigating the regulatory role of endothelial KLF11 in BBB preservation and neurovascular protection after ischemic stroke. EC- targeted overexpression of KLF11 significantly mitigated BBB leakage in ischemic brains, evidenced by significantly reduced extravasation of BBB tracers and infiltration of peripheral immune cells, and less brain water content. Endothelial cell- selective KLF11 transgenic (EC- KLF11 Tg) mice also exhibited smaller brain infarct and improved neurological function in response to ischemic insults. Furthermore, EC- targeted transgenic overexpression of KLF11 preserved cerebral tight junction (TJ) levels and attenuated the expression of pro- inflammatory factors in mice after ischemic stroke. Mechanistically, we demonstrated that KLF11 directly binds to the promoter of major endothelial TJ proteins including occludin and ZO- 1 to promote their activities. Our data indicate that KLF11 functions at the EC level to preserve BBB structural and functional integrity, and therefore, confers brain protection in ischemic stroke. KLF11 may be a novel therapeutic target for the treatment of ischemic stroke and other neurological conditions involving BBB breakdown and neuroinflammation.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/155919/1/bpa12831_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155919/2/bpa12831.pd

A cohort study of the efficacy and safety of immune checkpoint inhibitors plus anlotinib versus immune checkpoint inhibitors alone as the treatment of advanced non-small cell lung cancer in the real world

BACKGROUND: Anlotinib is a new multi-target tyrosine kinase inhibitor (TKI) and has been shown to have antitumor effects and synergistic antitumor effects with immunotherapy only in animal studies and in the 2nd-line treatment in small clinical trials. A real-world study with large sample to compare the efficacy and safety of anlotinib plus immune checkpoint inhibitors (ICIs) with ICIs alone in the multiline treatment of advanced non-small cell lung cancer (NSCLC) was urgently needed. METHODS: The data of 535 advanced NSCLC patients were collected from January 1, 2018, to December 31, 2021. The patients were divided into 2 groups: (I) ICI monotherapy (230 patients); (II) ICI + anlotinib (305 patients). After propensity-score matching (PSM) to reduce the effects of biases and confounding variables, the progression-free survival time (PFS), occurrence of adverse events, disease control rate (DCR), and objective response rate (ORR) of the 2 groups were compared. The effects of clinical factors, including age, gender, gene mutations, tumor proportion score, metastases, and combined radiotherapy, were also analyzed. RESULTS: After PSM, the baseline clinical characteristics were well balanced and the 2 group had a good comparability. Patients in the ICI + anlotinib group had significantly longer median PFS in both the 2nd-line treatment (7.73 vs. 4.70 months; P=0.003) and 3rd-line treatment (5.90 vs. 3.37 months; P=0.020), but the difference lacked statistical significance in the 1st-line treatment (8.40 vs. 5.20 months; P=0.229). The overall median PFS of patients in the ICI + anlotinib group was also much longer than that of patients in the ICI monotherapy group (6.37 vs. 3.90 months; P<0.001). The ICI + anlotinib group also tended to have a higher DCR, a higher ORR, and a higher probability of severe adverse drug reactions during the treatment than the ICI monotherapy group, but the differences were not statistically significant. Combining ICI + anlotinib could improve the outcomes of patients with bone metastasis. CONCLUSIONS: Anlotinib + ICI therapy could have greater efficacy in the treatment of advanced NSCLC patients than ICI monotherapy. The probability of adverse events might increase in the combined treatment, but could be controlled

Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

Publisher Copyright: © 2022, The Author(s).Background: Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. Results: To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3–5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. Conclusions: Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.Peer reviewe

Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

Funding GMP, PN, and CW are supported by NHLBI R01HL127564. GMP and PN are supported by R01HL142711. AG acknowledge support from the Wellcome Trust (201543/B/16/Z), European Union Seventh Framework Programme FP7/2007–2013 under grant agreement no. HEALTH-F2-2013–601456 (CVGenes@Target) & the TriPartite Immunometabolism Consortium [TrIC]-Novo Nordisk Foundation’s Grant number NNF15CC0018486. JMM is supported by American Diabetes Association Innovative and Clinical Translational Award 1–19-ICTS-068. SR was supported by the Academy of Finland Center of Excellence in Complex Disease Genetics (Grant No 312062), the Finnish Foundation for Cardiovascular Research, the Sigrid Juselius Foundation, and University of Helsinki HiLIFE Fellow and Grand Challenge grants. EW was supported by the Finnish innovation fund Sitra (EW) and Finska Läkaresällskapet. CNS was supported by American Heart Association Postdoctoral Fellowships 15POST24470131 and 17POST33650016. Charles N Rotimi is supported by Z01HG200362. Zhe Wang, Michael H Preuss, and Ruth JF Loos are supported by R01HL142302. NJT is a Wellcome Trust Investigator (202802/Z/16/Z), is the PI of the Avon Longitudinal Study of Parents and Children (MRC & WT 217065/Z/19/Z), is supported by the University of Bristol NIHR Biomedical Research Centre (BRC-1215–2001) and the MRC Integrative Epidemiology Unit (MC_UU_00011), and works within the CRUK Integrative Cancer Epidemiology Programme (C18281/A19169). Ruth E Mitchell is a member of the MRC Integrative Epidemiology Unit at the University of Bristol funded by the MRC (MC_UU_00011/1). Simon Haworth is supported by the UK National Institute for Health Research Academic Clinical Fellowship. Paul S. de Vries was supported by American Heart Association grant number 18CDA34110116. Julia Ramierz acknowledges support by the People Programme of the European Union’s Seventh Framework Programme grant n° 608765 and Marie Sklodowska-Curie grant n° 786833. Maria Sabater-Lleal is supported by a Miguel Servet contract from the ISCIII Spanish Health Institute (CP17/00142) and co-financed by the European Social Fund. Jian Yang is funded by the Westlake Education Foundation. Olga Giannakopoulou has received funding from the British Heart Foundation (BHF) (FS/14/66/3129). CHARGE Consortium cohorts were supported by R01HL105756. Study-specific acknowledgements are available in the Additional file 32: Supplementary Note. The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute; the National Institutes of Health; or the U.S. Department of Health and Human Services.Peer reviewedPublisher PD

Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

Abstract Background Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. Results To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3–5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. Conclusions Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk